urate lowering therapies and left ventricular diastolic dysfunction

Conditions: Hyperuricemia; Metabolic Syndrome; Left Ventricular Diastolic Dysfunction

Summary: hyperuricemia is an additional risk factor for cardiovascular disease, associating with left ventricular diastolic dysfunction in individuals with metabolic syndrome. the effect of urate-lowering therapies on left ventricular diastolic dysfunction remains unclear. the study is conducted to investigate whether febuxostat or benzbromarone might improve left ventricular diastolic dysfunction in individuals with metabolic syndrome and hyperuricemia

between 1, july 2018 and 31, dec 2018, consecutive individuals with metabolic syndrome hyperuricemia are candidates of the present study. after the eligible candidates sign the informed consent, they will receive blood tests with a fasting time of 8 hours at least. the investigators will randomize the study participants by pre-specified random codes with a 1:1:1 ratio to the three groups. the study medication, febuxostat or benzbromarone, will be administered orally on the next day after transthoracic echocardiography is performed. the control group will only receive dietary control. all participant will receive transthoracic echocardiography and blood tests at baseline and at 3 months. the visit will be scheduled at baseline and at the 3rd month. the blood tests include high-sensitivity c-reactive protein, high-sensitivity interleukin-1 beta, high-sensitivity interleukin-6, tumor necrosis factor alpha, dickkopf-related protein 3, galectin-3, st2, fibroblast growth factor 23, xanthine oxidase activity, and thioredoxin.

Eligibility criteria:
inclusion criteria (all of the four criteria) 1. aged between 40-75 years 2. metabolic syndrome 3. hyperuricemia, defined as a serum uric acid level of 7 mg/dl or more in men or 6 mg/dl or more in females, with a history of hyperuricemia within a year; or a serum uric acid level of 8 mg/dl or more in men or 7 mg/dl or more in females and it is hardly expected to be modified by dietary control; or persistent hyperuricemia after dietary control for 3 months 4. not take any of urate-lowering therapies (benzbromarone, allopurinol, or febuxostat) exclusion criteria: 1. pregnancy 2. hypersensitivity to febuxostat or benzbromarone 3. acute gout 4. a history of urinary tract stone 5. chronic kidney disease stage iv or v 6. valvular heart disease with moderate or severe regurgitation 7. left ventricular ejection fraction of 40% or less 8. hypertrophic cardiomyopathy or dilated cardiomyopathy or infiltrative cardiomyopathy or constrictive cardiomyopathy 9. a history of congenital heart disease 10. a history of pulmonary hypertension 11. chronic atrial fibrillation or significant arrhythmia 12. a history of intracardiac device implantation 13. uncontrolled hypertension (systolic blood pressure \> 160mm hg or diastolic blood pressure \> 100 mm hg) 14. alanine aminotransferase \> 3 times upper limit) 15. acute infection 16. suspected or diagnosed with malignancy 17. a history of autoimmune disease 18. limited to or dependent on daily activities 19. life expectancy less than a year 20. acute coronary syndrome or received a percutaneous coronary intervention or received a coronary artery graft bypass surgery or stroke within 3 months 21. diabetes with insulin treatment or glucagon-like peptide 1 receptor agonist treatment 22. anemia (hemoglobin \< 11 mg/dl in mem or \<10mg/dl in women)

Keywords: serum uric acid metabolic syndrome left ventricular diastolic dysfunction febuxostat benzbromarone